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Vitamin supplementation in disease prevention

Kathleen M Fairfield, MD, DrPH
Section Editor
Timothy O Lipman, MD
Deputy Editor
H Nancy Sokol, MD


Vitamins are chemically unrelated families of organic compounds that are essential in small amounts for normal metabolism. Because vitamins (with the exception of vitamin D) cannot be synthesized by humans, they need to be ingested in the diet to prevent disorders of metabolism. They should be distinguished from minerals (such as calcium and iron), some of which are also essential micronutrients.

When vitamin deficiency is defined as low blood levels, or levels associated with reversible metabolic changes, the prevalence of vitamin deficiency on typical Western diets is higher than generally believed, especially in older adults. Pregnancy and alcohol consumption may increase requirements for some vitamins. Subtle deficiencies in several vitamins, at levels below those causing classic vitamin deficiency syndromes (eg, scurvy or pellagra), have been associated with chronic diseases such as atherosclerosis, cancer, and osteoporosis in observational studies. However, it is less well-established that the vitamins in supplements can prevent or reverse chronic diseases.

Studies of the effects of vitamins have tended to disagree with each other. This is partly because subsequent randomized trials have contradicted prior, more fallible, observational studies. Additionally, studies of vitamin effects have often not taken into account baseline vitamin status and dose, both of which are critical determinants of biologic effects [1].

Genetic factors may affect how vitamins are metabolized and the consequences of supplementation in various clinical situations and doses. Not enough is yet known to use genetic information to guide clinical decisions about vitamin dose and deficiencies, but that information is likely to become available.

The evidence for using vitamin supplementation to prevent chronic disease is reviewed here. The potential benefits of vitamin supplementation in specific disease conditions are discussed on topics about those conditions. Overviews of individual vitamins, dietary minerals, and dietary supplements are also discussed separately. (See "Overview of water-soluble vitamins" and "Overview of vitamin A" and "Overview of vitamin D" and "Overview of vitamin E" and "Overview of dietary trace minerals" and "Overview of herbal medicine and dietary supplements".)


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Literature review current through: Sep 2016. | This topic last updated: Mar 21, 2016.
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  1. Heaney RP. Vitamin D--baseline status and effective dose. N Engl J Med 2012; 367:77.
  2. Oakley GP Jr. Eat right and take a multivitamin. N Engl J Med 1998; 338:1060.
  3. Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008; 87:517.
  4. Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet 2004; 125C:12.
  5. Czeizel AE, Medveczky E. Periconceptional multivitamin supplementation and multimalformed offspring. Obstet Gynecol 2003; 102:1255.
  6. Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can 2006; 28:680.
  7. Botto LD, Mulinare J, Erickson JD. Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps. Am J Med Genet A 2003; 121A:95.
  8. Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999; 341:1485.
  9. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998; 129:517.
  10. Giovannucci E, Rimm EB, Ascherio A, et al. Alcohol, low-methionine--low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 1995; 87:265.
  11. Lewis SJ, Harbord RM, Harris R, Smith GD. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst 2006; 98:1607.
  12. Larsson SC, Giovannucci E, Wolk A. Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 2007; 99:64.
  13. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007; 297:2351.
  14. Logan RF, Grainge MJ, Shepherd VC, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2008; 134:29.
  15. Ebbing M, Bønaa KH, Nygård O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009; 302:2119.
  16. Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA 2008; 300:2012.
  17. Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 2013; 381:1029.
  18. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 2006; 296:2720.
  19. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007; 369:1876.
  20. Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 2009; :CD006612.
  21. Miller ER 3rd, Juraschek S, Pastor-Barriuso R, et al. Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease and risk interaction with baseline homocysteine levels. Am J Cardiol 2010; 106:517.
  22. Lee M, Hong KS, Chang SC, Saver JL. Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis. Stroke 2010; 41:1205.
  23. Forman JP, Rimm EB, Stampfer MJ, Curhan GC. Folate intake and the risk of incident hypertension among US women. JAMA 2005; 293:320.
  24. Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999; 69:564.
  25. Berner B, Odum L, Parving A. Age-related hearing impairment and B vitamin status. Acta Otolaryngol 2000; 120:633.
  26. Institute of Medicine. Report at a Glance, Report Brief: Dietary reference intakes for calcium and vitamin D, released 11/30/2010. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Report-Brief.aspx (Accessed on December 01, 2010).
  27. US Preventive Services Task Force. Screening for vitamin D deficiency: draft recommendation statement. AHRQ publication no 13-05183-EF-2. http://www.uspreventiveservicestaskforce.org/draftrec.htm (Accessed on July 15, 2014).
  28. Marriott BM. Vitamin D supplementation: a word of caution. Ann Intern Med 1997; 127:231.
  29. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA 2004; 291:1999.
  30. Jackson C, Gaugris S, Sen SS, Hosking D. The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM 2007; 100:185.
  31. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 2009; 339:b3692.
  32. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 2009; :CD007146.
  33. Cameron ID, Murray GR, Gillespie LD, et al. Interventions for preventing falls in older people in nursing care facilities and hospitals. Cochrane Database Syst Rev 2010; :CD005465.
  34. Institute of Medicine Dietary reference intakes of calcium and vitamin D, National Academy Press, Washington, DC 2011.
  35. Manson JE, Mayne ST, Clinton SK. Vitamin D and prevention of cancer--ready for prime time? N Engl J Med 2011; 364:1385.
  36. Meyer HE, Holvik K, Lips P. Should vitamin D supplements be recommended to prevent chronic diseases? BMJ 2015; 350:h321.
  37. Diaz MN, Frei B, Vita JA, Keaney JF Jr. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997; 337:408.
  38. Jha P, Flather M, Lonn E, et al. The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 1995; 123:860.
  39. Stanner SA, Hughes J, Kelly CN, Buttriss J. A review of the epidemiological evidence for the 'antioxidant hypothesis'. Public Health Nutr 2004; 7:407.
  40. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364:1219.
  41. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361:2017.
  42. Schürks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 2010; 341:c5702.
  43. Ascherio A, Rimm EB, Hernán MA, et al. Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med 1999; 130:963.
  44. Bjelakovic G, Nikolova D, Gluud LL, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012; :CD007176.
  45. Boo NY, Arshad AR. A study of cleft lip and palate in neonates born in a large Malaysian maternity hospital over a 2-year period. Singapore Med J 1990; 31:59.
  46. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330:1029.
  47. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 334:1150.
  48. Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003; 290:476.
  49. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996; 334:1145.
  50. Lee IM, Cook NR, Manson JE, et al. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst 1999; 91:2102.
  51. Lin J, Cook NR, Albert C, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst 2009; 101:14.
  52. Kushi LH, Fee RM, Sellers TA, et al. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol 1996; 144:165.
  53. Hunter DJ, Manson JE, Colditz GA, et al. A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 1993; 329:234.
  54. Zhang S, Hunter DJ, Forman MR, et al. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 1999; 91:547.
  55. Tamimi RM, Hankinson SE, Campos H, et al. Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol 2005; 161:153.
  56. Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med 1994; 331:141.
  57. Marshall JR. Beta-carotene: a miss for epidemiology. J Natl Cancer Inst 1999; 91:2068.
  58. Fawzi WW, Chalmers TC, Herrera MG, Mosteller F. Vitamin A supplementation and child mortality. A meta-analysis. JAMA 1993; 269:898.
  59. Butler JC, Havens PL, Sowell AL, et al. Measles severity and serum retinol (vitamin A) concentration among children in the United States. Pediatrics 1993; 91:1176.
  60. Melhus H, Michaëlsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998; 129:770.
  61. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002; 287:47.
  62. Michaëlsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med 2003; 348:287.
  63. Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995; 333:1369.
  64. Coulter ID, Hardy ML, Morton SC, et al. Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer. J Gen Intern Med 2006; 21:735.
  65. Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 2009; 301:52.
  66. Wang L, Sesso HD, Glynn RJ, et al. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. Am J Clin Nutr 2014; 100:915.
  67. Thomas LD, Elinder CG, Tiselius HG, et al. Ascorbic acid supplements and kidney stone incidence among men: a prospective study. JAMA Intern Med 2013; 173:386.
  68. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142:37.
  69. Chan JM, Stampfer MJ, Ma J, et al. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 1999; 8:893.
  70. Kirsh VA, Hayes RB, Mayne ST, et al. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst 2006; 98:245.
  71. Woodson K, Tangrea JA, Barrett MJ, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst 1999; 91:1738.
  72. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294:56.
  73. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005; 293:1338.
  74. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301:39.
  75. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90:440.
  76. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306:1549.
  77. Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 2000; 54:1265.
  78. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002; 287:3223.
  79. Morris MC, Evans DA, Bienias JL, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002; 287:3230.
  80. Yaffe K, Clemons TE, McBee WL, et al. Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial. Neurology 2004; 63:1705.
  81. Kang JH, Cook N, Manson J, et al. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med 2006; 166:2462.
  82. Meydani SN, Meydani M, Blumberg JB, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA 1997; 277:1380.
  83. Serafini M. Dietary vitamin E and T cell-mediated function in the elderly: effectiveness and mechanism of action. Int J Dev Neurosci 2000; 18:401.
  84. Girodon F, Galan P, Monget AL, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med 1999; 159:748.
  85. Meydani SN, Leka LS, Fine BC, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA 2004; 292:828.
  86. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA 2002; 288:715.
  87. Glynn RJ, Ridker PM, Goldhaber SZ, et al. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation 2007; 116:1497.
  88. Omenn GS, Beresford SA, Motulsky AG. Preventing coronary heart disease: B vitamins and homocysteine. Circulation 1998; 97:421.
  89. Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging 2002; 6:39.
  90. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA 2010; 303:1077.
  91. Zhang SM, Willett WC, Selhub J, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 2003; 95:373.
  92. Clarke R, Grimley Evans J, Schneede J, et al. Vitamin B12 and folate deficiency in later life. Age Ageing 2004; 33:34.
  93. Vogel T, Dali-Youcef N, Kaltenbach G, Andrès E. Homocysteine, vitamin B12, folate and cognitive functions: a systematic and critical review of the literature. Int J Clin Pract 2009; 63:1061.
  94. Stabler SP, Lindenbaum J, Allen RH. Vitamin B-12 deficiency in the elderly: current dilemmas. Am J Clin Nutr 1997; 66:741.
  95. Dary O. Establishing safe and potentially efficacious fortification contents for folic acid and vitamin B12. Food Nutr Bull 2008; 29:S214.
  96. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008; :CD004514.
  97. Guallar E, Stranges S, Mulrow C, et al. Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann Intern Med 2013; 159:850.
  98. Huang HY, Caballero B, Chang S, et al. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med 2006; 145:372.
  99. Fortmann SP, Burda BU, Senger CA, et al. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013; 159:824.
  100. Grodstein F, O'Brien J, Kang JH, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med 2013; 159:806.
  101. Christen WG, Glynn RJ, Manson JE, et al. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2014; 121:525.
  102. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr 2009; 89:693S.
  103. Davey GK, Spencer EA, Appleby PN, et al. EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. Public Health Nutr 2003; 6:259.
  104. Outila TA, Kärkkäinen MU, Seppänen RH, Lamberg-Allardt CJ. Dietary intake of vitamin D in premenopausal, healthy vegans was insufficient to maintain concentrations of serum 25-hydroxyvitamin D and intact parathyroid hormone within normal ranges during the winter in Finland. J Am Diet Assoc 2000; 100:434.
  105. U.S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 150:626.
  106. Moyer VA, U.S. Preventive Services Task Force. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive services Task Force recommendation statement. Ann Intern Med 2014; 160:558.
  107. NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention. NIH Consens State Sci Statements 2006; 23:1.